ABSTRACT Race, multiple myeloma (MM), and anti-cancer treatments are independent risk factors for venous thromboembolism (VTE). The synergistic effects of these factors on the long term risk of VTE among patients with MM are not well documented. Greater clinical evidence on the racial differences in risk of VTE following diagnosis and treatment of MM is a critical first step in developing effective prevention strategies for high risk subgroups. The long term goal of the proposed research is to better understand the racial differences in anti- cancer treatment-related cardiotoxicity; the overall objective of this R21 application is to determine the risk of VTE among patients following MM diagnosis and treatment by race in (i) a large retrospective population- based cohort study of MM patients from the SEER-Medicare linked database and a matched non-cancer cohort; and (ii) a pooled multi-institutional cohort study of MM patients undergoing bone marrow transplant and detailed information on other prognostic indicators, including biomarkers, cytogenetics and prior treatment response. The central hypothesis is that the burden of MM diagnosis and associated treatment-related cardiotoxicity is different for racial and ethnic minority populations of African Americans, Asian Pacific Islanders, and Hispanics compared to non-Hispanic Whites. This objective will be accomplished by pursuing the following two specific aims: Aim 1) Determine differences in long-term risk of VTE following diagnosis and treatment of MM by race (a) compare VTE incidence in MM patients and matched non-cancer counterparts (b) compare racial differences in cardiotoxicity associated with MM treatments; and Aim 2) Investigate racial differences in risk factors for VTE among MM patients receiving bone marrow transplant in a pooled multi- institutional cohort study. This work is innovative because it will be the first study to determine racial differences in long-term treatment-related cardiotoxicity in MM using population-based data in the United States. Moreover, we propose a robust methodological approach to estimate VTE incidence that minimizes biases arising from not accounting for events that modify the risk of VTE (cardiovascular comorbidities) or preclude its observation (death) in this population. This research is significant because it leverages epidemiologic study designs with data resources from population-based cancer registries, administrative claims and two institutional MM cohort studies. Ultimately, this comprehensive evaluation of racial differences in treatment-related VTE among patients with MM is an important first step toward larger studies developing and evaluating approaches to prevention and mitigation of cardiotoxicity associated with cancer treatment.